Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by arthritis and nephritis, circulating immune complexes and autoantibodies, polyclonal B-cell hyperactivity and depressed cell-mediated immunity. Most patients with active SLE also have high levels of an unusual acid-labile form of human leukocyte (alpha) interferon (IFN) in their serum. A similar alpha IFN has been found in patients with vasculitis, rheumatoid arthritis and the acquired immunodeficiency syndrome (AIDS), but not in patients with drug-induced lupus-like syndromes. Whether the specific elevation of this particular acid-labile alpha IFN is a cause or an effect of autoimmune disease remains to be elucidated. Many studies have shown that IFN has diverse effects on the immune system, but the response of normal human lymphocytes to conventional human alpha IFN, which contains little if any of the acid-labile alpha IFN that predominates in SLE patients, may not accurately reflect the effects of 'autoimmune' IFN on cells from patients genetically predisposed to develop autoimmune disease. The objectives of this research project are to further characterize this novel human alpha IFN and to test the hypothesis that endogenous production of IFN contributes to immune disorders in patients with SLE. Specifically, Sephadex chromatography and SDS-PAGE will be used to compare acid-labile alpha IFNs isolated from serum or plasma of different SLE and AIDS patients and partially purified on an antibody-affinity column. In vitro assays of immune function will then be used to compare the effects of "conventional" and acid-labile "autoimmune" alpha IFNs on mononuclear cells from both normal subjects and SLE patients. Spontaneous and polyclonally activated immunoglobulin synthesis and production of autoantibodies in the presence and absence of each IFN will be quantitated. The effect of acid-labile alpha IFN on in vitro sensitization of normal and autoimmune lymphocytes with TNP-haptenated particulate and soluble T-cell dependent and independent antigens will be investigated. T-cell proliferation and function in response to mitogens, and IFN-induced modulation of cell surface Beta-2 microglobulin and Fc-receptors for IgG and IgM will also be studied. Finally, we will compare the regulatory effects of reference and acid-labile alpha IFNs on the activity of normal and autoimmune NK cells, and determine whether autoimmune NK cells produce acid-labile alpha IFN.